The major focus of this application is based upon our conviction that a better understanding of the pathogenesis of periodontal disease can be gained through a more complete knowledge of the normal biology and pathobiology of the major cell types responsible for maintaining the integrity of the gingival and periodontal tissues. Although it is well established in the literature (including previous publications from this grant) that the inflammatory cell infiltrate, generated mainly by the immunologic defense of the host, is responsible for periodontal tissue destruction, there are numberous unanswered questions as to how and to what degree are the structure and function of the epithelial cells and fibroblasts altered by inflammation. We propose to use the latest methodologies for studying cell structure, i.e., freeze-fracture for cell-to-cell contacts and cell membrane-substrate interaction; EM auto-radiography of matrix secretion and turnover; freeze-fixation and freeze-substitution for study of epithelial permeability to water soluble tracers and cell-to-cell communication; double autoradiography for cell migration and cell-mediated organization of connective tissue fibers; and EM morphometrics of cytoplasmic organelles. We will apply these methods to both healthy and diseased tissues. The achievement of the specific aims of this project will have direct application to the understanding of the pathogenesis of periodontal destruction as well as to the broader aspects of connective tissue morphogenesis and mucosal permeability.